Pregnanolones and method for producing the same from pregnandiones



Patented Apr. 8, 1941 UNITED 2,237,410 orricr.

PREGNANOLONES AND METI IOD FOR PRO- DUCING THE SAME FROM PREGNAN- DIONESAdolf Butenandt, Berlin-Dahlem, Germany, assignor, by mesnc assignments,to Schering Corporation, Bloomfield, N. .L, a corporation of New JerseyNo Drawing. Original application December 24,

1934, Serial No. 759,115. Divided and this application April 10, 1939,Serial No. 267,181. In

Germany December 23, 1933 (Granted under the provisions of sec. 14, actof March 2, 1927; 357 G.

7 Claims.

This invention relates to organic compounds of thecyclopentanopolyhydrophenanthrene series and more particularly topregnanolones and their derivatives, such as their esters, and to amethod of producing such compounds.

The present application is a division of my application Serial No,759,115, filed December 24, 1934.

In accordance with the present invention, a pregnandiol, produced orobtained in any known or suitable manner, is first oxidized topregnandion and the latter is then converted into pregnanolon by partialreduction which is carried out in such a manner that only one keto groupis reduced to an alcohol group.

The first phase of this method, the oxidation of the pregnandiol topregnandion, has already been carried out and described by me (Berichteder deutschen chem. Gesellschaft, vol. 63, p. 662/63) where also thecomplete reduction of pregnandion to pregnan by means of concentratedhydrochloric acid and zinc amalgam while heating, is described (I. c.vol. 64, page 2536). The partial reduction of pregnandion topregnanolon, however, was successful for the first time by the processclaimed herein. The partial reduction can not only be carried out bymeans of catalytically or otherwise activated hydrogen but also bytreatment of the pregnandion in the presence of catalysing agents withcompounds that are capable of yielding hydrogen while at the same timeforming their corresponding oxidation products, such as tetralin,cyclohexanol etc.

The pregnanolones represent valuable intermediate products for theproduction of compounds of therapeutic value, such as the hormone of themale germinal gland.

The invention will be described in detail with the aid of the followingexample which is presented by way of illustration only and not asindicating the limits of the invention.

Example 1 g, of pregnancliol is oxidized according to the methodheretofore described by me in the publication above referred to, in 40com. of 90% glacial acetic acid solution with an equal weight of chromicacid anhydride in 40 com. of glacial acetic acid. in the cold wherebythe pregnandion of the melting point 123 C. is obtained.

0.5 g. of said pregnandicn is treated, according to Willstaettersmethod, in 100 com. of glacial acetic acid in the cold with platinum andhydrogen until a quantity of hydrogen is absorbed necessary for thereduction of one carbonyl group. The reduction product, chieflypregnanolon 0211-13402, has, after recrystallization from alcohol, amelting point of 142 C.

The partial reduction may be carried out also by means of hydrogen inthe presence of other catalysts or even with hydrogen in statu nascendior with atomic hydrogen.

As starting material there may be used not only the pregnandiol as it isisolated as by-prodnot in the production of follicle hormone from urinebut also other pregnandiols obtained synthetically.

Thus, for instance, allo-pregnandiol may be converted intoallo-pregnanolon by the same procedure as described in the example.

The pregnanolon obtained as above described has the general formula0211-13402 and can be converted to the ester, ether, chloride, etc, likeother alcohols by methods known in the art. The process ordinarilyyields both pregnanol- 3-one-2O and pregnanol-20-one-3 which can beseparated as such by known methods, or by taking advantage of thedifferent properties of their derivatives, such, as the esters,condensation; products with keto reagents, etc.

Various modifications in the process and reagents may be resorted towithin the scope of the appended claims without departing from theprinciples set forth herein.

What I claim is:

1. The method of producing pregnanolones which comprises partiallyreducing a pregnandione to convert one of the keto groups to analcoholic group, and isolating the hydroxy ketone so obtained.

2. The method of producing pregnanolones which comprises partiallyreducing a pregnana dione with the aid of hydrogen and a hydrogenationcatalyst in the cold to convert one of the keto groups to an alcoholicgroup, and isolating the hydroxy ketone so obtained.

3. A method for the production of a pregnanolon of the formula0211-13402 comprising oxidizing a pregnandiol to the correspondingpregnandione and partially reducing said pregnandione to thecorresponding pregnanolon.

4. A method for the production of a pregnanolon of the formula 021113402comprising subjecting pregnandione to partial hydrogenation withcatalytically activated hydrogen.

5. A. method for the production of a pregnanolon of the formula021113402 comprising subjecting pregnandione to partial hydrogenationwith hydrogen in the presence of a hydrogenation catalyst.

6 A method for the production of a pregnanolon of the formula C21H34Oecomprising subjecting pregnandione to partial hydrogenation with acompound capable of yielding hydrogen while at the same time formingtheir corresponding oxidation products.

7. A method for the production of a pregnanolon of the formula(2211-13402 comprising treating a solution of pregnandione in aceticacid in the cold with hydrogen in the presence of platinum until thequantity of hydrogen is absorbed which is necessary for the reduction ofone carbonyl group.

ADOLF BUTENANDT.

